Problem: Pneumonia is the leading cause of death worldwide. Even in developed countries, it continues to be the leading cause of death from infection and a serious complication for patients being treated for other diseases. The threat of lung infections is elevated when there is a decreased level of host resistance (e.g. immunocompromised cancer patients) and when there is an increased level of pathogen exposure (e.g. pandemics, bioterror, and biowarfare). Acute leukemia patients are currently some of the most at-risk patients, as they are faced with significant immunocompromise resulting from their cancer treatments. Many times these risks prevent the full cancer treatment plan from being completed. As a result, each year an estimated 44,700 leukemia patients spend more than one-half billion dollars on a range of treatments in an effort to prevent pneumonia. Pulmotect's Solution: Pulmotect has identified and is developing a novel technology to address the risks of inhaled microbes. Our therapeutic (PUL-042) is a combination of two TLR ligands that stimulate the lung's own innate defense mechanisms to create a hostile environment for pathogens and reduce or prevent infection. Both in vitro and in vivo experiments have been completed to validate this technology. Importantly, because of the low cell-turnover rate, the lung epithelium is resistant to chemotherapy drugs so the innate immune response remains intact. It is in these most at-risk patients where proof-of-concept can be captured for additional markets. The focus of this proposal is to accomplish key milestones that will validate this technology for commercialization. This SBIR application is focused on addressing important preclinical important issues. The three Aims included are designed to validate and expand upon the proof-of-concept data already obtained. The Aims are focused for transitioning this technology into the clinic. Achieving these milestones would provide significant data for an IND application for a product that is safe and efficacious. Positive results from this phase I proposal would potentially lead to a phase II SBIR application to perform an in-depth study of the therapy in a second animal model, including FDA approved safety and toxicity studies. Additionally, by demonstrating subsequent discoveries in Pulmotect's pipeline, additional outside funds from investors can better be pursued to transition this technology into the clinic and market place. Overall, the outlined milestones of this proposal would build upon previous work, add to the foundation of this platform technology, and help bring this technology to the clinic. ) PUBLIC HEALTH RELEVANCE: Pulmotect, Inc is developing novel therapeutics that stimulates the innate immune system to protect against infectious diseases, even in cases of severely compromised immunity. Proof-of-concept data has shown that this technology effectively protects against a broad range of inhaled pathogens. This project will provide significant data to help transition this technology from the lab to the clinic, where physicians are asking to use the technology to benefit their patients.